# IDO-Mediated Immune and Metabolic Dysregulation in Schwann Cells Exposed to Mycobacterium leprae

## TL;DR

This study explores how Mycobacterium leprae affects Schwann cells through IDO, an enzyme linked to immune and metabolic changes, suggesting IDO as a potential treatment target for leprosy.

## Contribution

The novel contribution is identifying IDO's role in Schwann cell immune and metabolic dysregulation during M. leprae infection and its therapeutic potential.

## Key findings

- M. leprae induces IDO expression in Schwann cells, linking it to immune modulation and neuropathy.
- IDO inhibition with 1-MT reduces Schwann cell viability and metabolic activity during infection.
- IDO1 inhibition upregulates antioxidant genes like GPX4, NFE2L2, and HMOX1 in infected Schwann cells.

## Abstract

Leprosy is a chronic infectious disease that targets the peripheral nervous system, leading to peripheral neuropathy. Mycobacterium leprae primarily infects Schwann cells, adipocytes, and macrophages, altering their metabolism and gene expression. This study investigates the metabolic interaction between M. leprae and Schwann cells, with a focus on indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan catabolism via the kynurenine pathway. We found that M. leprae induces IDO expression in Schwann cells, suggesting a role in immune modulation and neuropathy. Inhibition of IDO with 1-methyl-L-tryptophan (1-MT) reduced Schwann cell viability and metabolic activity in response to M. leprae. After 24 h of infection, M. leprae impaired mitochondrial membrane potential, although no significant changes in autophagy or mitochondrial ultrastructure were observed by electron microscopy. Interestingly, IDO1 inhibition upregulated the expression of antioxidant genes, including GPX4, NFE2L2, and HMOX1. In conclusion, these findings highlight a central role for IDO in shaping the metabolic and immunological response of Schwann cells to M. leprae infection. IDO induction contributes to immune regulation and cellular stress, while its inhibition disrupts cell viability and promotes antioxidant gene expression. These results position IDO as a potential therapeutic target for modulating host–pathogen interactions and mitigating nerve damage in leprosy.